SHP099 單鹽酸鹽
SHP099 hydrochloride是有效，選擇性，有口服活性的 SHP2 抑制劑，IC50值為70 nM。
生物活性
SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC50 of 70 nM[1].
IC50 & Target
IC50: 70 nM (SHP2)[1]
體外研究(In Vitro)
The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells[2].
體內(nèi)研究(In Vivo)
After a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg[1].
分子量：388.72
性狀：Solid
Formula：C16H20Cl3N5
CAS 號(hào)：2200214-93-1
運(yùn)輸條件
Room temperature in continental US; may vary elsewhere.
儲(chǔ)存方式
4°C, sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性數(shù)據(jù)
In Vitro:
DMSO : 4.1 mg/mL (10.55 mM; Need ultrasonic and warming)
H2O : ≥ 2.5 mg/mL (6.43 mM)
* "≥" means soluble, but saturation unknown.
| 1 mM | 2.5725 mL | 12.8627 mL | 25.7255 mL |
| 5 mM | 0.5145 mL | 2.5725 mL | 5.1451 mL |
| 10 mM | 0.2573 mL | 1.2863 mL | 2.5725 mL |
請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)月內(nèi)使用，-20°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)月內(nèi)使用。
請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥方式選擇適當(dāng)?shù)娜芙夥桨?。以下溶解方案都?qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶
- 1.
請(qǐng)依序添加每種溶劑： 50% PEG300 50% saline
Solubility: 20 mg/mL (51.45 mM); Suspended solution; Need ultrasonic
- 2.
請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (6.43 mM); Clear solution
參考文獻(xiàn)
[1]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. [Content Brief]
[2]. Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. [Content Brief]
[3]. Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018.
注：產(chǎn)品僅用于科研
采購(gòu)中心
